This invention relates to a novel process for preparing 4-aminopyridines wherein the amino group in the 4-position is present in free or substituted form.
The products of this process are acylating catalysts and are intermediates for the production of active medicinal agents. Typical of medicinally active agents obtained from 4-aminopyridine are esters of steroidal hydroxyl groups e.g. DOS No. 2,137,856 (German Unexamined Laid-Open Application).
In selective or rapid acylation of amines (see, L. M. Litvinenko et al., Chem. Abs. 68, 68325u (1968) and alcohols (see, W. Steglich and G. Hoefle, "Angew. Chemie" 81, 1001 (1969); Tetrahedron Letters 4727 (1970); and Synthesis, 1972, 619), customary acylating catalysts are 4-dialkylaminopyridines, especially 4-dimethylaminopyridine as disclosed in DOS No. 1,958,954 and DOS No. 2,137,856. Known methods for the preparation of substituted 4-aminopyridines are unreliable. Required starting materials can be prepared only be several, expensive steps, for example, amination of 4-chloropyridine with dimetylamine at 150.degree. C. under pressure, L. Pentimalli, Gazz. Chim. Ital. 94, 902 (1964); reaction of silylated 4pyridone with amines, such as pyrrolidine, using acidic catalysis, H. Vorbrueggen, "Angew. Chemie" 84, 348 (1972). or conversion of 4-pyridylphenyl ether by reaction with secondary amines to the corresponding 4-dialkylaminopyridines, D. Jerchel et al., al., "Chem. Ber." 91 1266 (1958).
It has been found in accordance with this invention that 4-aminopyridines can be prepared, in a technically feasible method, simply and directly from readily accessible 4-pyridylpyridinium chloride or a salt thereof, preferably the hydrochloride, by reaction with an easily obtainable acid amide.